17β-Estradiol reverses shear-stress-mediated low density lipoprotein modifications

Juliana Hwang, Mahsa Rouhanizadeh, Ryan T. Hamilton, Tiantian C. Lin, Jason P. Eiserich, Howard N. Hodis, Tzung K. Hsiai

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Within arterial bifurcations or branching points, oscillatory shear stress (OSS) induces oxidative stress mainly via the reduced nicotinamide adenine dinucleodtide phosphate (NADPH) oxidase system. It is unknown whether 17β-estradiol (E2) can regulate OSS-mediated low-density lipoprotein (LDL) modifications. Bovine aortic endothelial cells were pretreated with E2 at 5 nmol/L, followed by exposure to OSS (0 ± 3.0 dynes/cm2 s and 60 cycles/min) in a flow system. E2 decreased OSS-mediated NADPH oxidase mRNA expression, and E2-mediated {radical dot}NO production was mitigated by the NO synthase inhibitor N(G)-nitro-l-argenine methyl ester. The rates of O2 -{radical dot} production in response to OSS increased steadily as determined by superoxide-dismutase-inhibited ferricytochrome c reduction; whereas, pretreatment with E2 decreased OSS-mediated O2 -{radical dot} production (n = 4, p < 0.05). In the presence of native LDL (50 μg/mL), E2 also significantly reversed OSS-mediated LDL oxidation as determined by high-performance liquid chromatography. In the presence of O2 -{radical dot} donor, xanthine oxidase (XO), E2 further reversed XO-induced LDL lipid peroxidation (n = 3, p < 0.001). Mass spectra acquired in the m/z 400-1800 range, revealed XO-mediated LDL protein nitration involving tyrosine 2535 in the α-2 domains, whereas pretreatment with E2 reversed nitration, as supported by the changes in nitrotyrosine intensities. Thus, E2 plays an indirect antioxidative role. In addition to upregulation of endothelial {radical dot}NO synthase and downregulation of Nox4 expression, E2 influences LDL modifications via lipid peroxidation and protein nitration.

Original languageEnglish (US)
Pages (from-to)568-578
Number of pages11
JournalFree Radical Biology and Medicine
Volume41
Issue number4
DOIs
StatePublished - Aug 15 2006

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Keywords

  • 17β-Estradiol
  • LDL lipid oxidation and nitration
  • NADPH oxidase
  • Nitric oxide
  • Shear stress
  • Superoxide anion

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Hwang, J., Rouhanizadeh, M., Hamilton, R. T., Lin, T. C., Eiserich, J. P., Hodis, H. N., & Hsiai, T. K. (2006). 17β-Estradiol reverses shear-stress-mediated low density lipoprotein modifications. Free Radical Biology and Medicine, 41(4), 568-578. https://doi.org/10.1016/j.freeradbiomed.2006.04.010